Garding IL-8 and TNF-, only magnolol considerably lowered their secretion in stimulated human neutrophils (Figure 5b,c). The capacity of honokiol and magnolol to inhibit the release of pro-inflammatory cytokines is well-known, and derives from in vitro, ex vivo and in vivo studies [11,12]. Nonetheless, by comparing our outcomes with these obtained in related experimental models, a single should note that the outcomes vary depending on several elements, which include the cell type, the agent used for cytokine generation as well as the remedy situations (honokiol and magnolol concentrations, and period of incubation). For instance, Wang et al. [41] assessed the potency of honokiol to inhibit IL-1 and IL-8 generation by TNF- in an ex vivo human neutrophils model. After a 24 h incubation with honokiol (up to ten ), a concentration-dependent inhibition of IL-1 and IL-8 expression was observed. Furthermore, Li et al. [42] demonstrated that honokiol was able to inhibit IL-1 and TNF- release in ex vivo LPS-activated human monocyte-derived dendritic cells, and therapy for 48 h with honokiol (concentration selection of 18.755 ) decreased both cytokines’ production compared to the untreated manage. Liu et al. [43] showed that magnolol at 10 reduced IL-8 generation in ex vivo human gingival fibroblasts upon stimulation with advanced glycation finish products. Overall, thinking of the observed antidermatophytic activity, alongside the inhibitory effects of pro-inflammatory cytokine release, the additional development of formulations which includes honokiol, magnolol and their combinations with terbinafine is justified. Nevertheless, like other all-natural phenolics, the pharmaceutical application of honokiol and magnolol may be hampered by their low water solubility and chemical instability [14]. Hence, the inclusion in delivery systems which include cyclodextrins, micelles and liposomes could be an method towards overcoming such limitations [11,44,45]. Besides, the mode of administration impacts the availability of honokiol and magnolol at the infection site. Therefore, a topical use of both neolignans and their combinations with terbinafine is quickly envisioned. Notwithstanding our observations, further research are necessary to assess no matter if the in vitro benefits translate into similar outcomes in in vivo settings and to fully elucidate the mechanism of antidermatophytic activity. four. Components and Solutions 4.1. Chemical compounds 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) (HEPES), 3-(N-morpholino) propanesulphonic acid (MOPS), acetonitrile, anhydrous glucose, chloramphenicol, cycloheximide, dimethyl sulfoxide (DMSO), dextran, ergosterol, ethanol, ethyl acetate, fetal bovine serum (FBS), formic acid, hexane, honokiol, L-glutamine, magnolol, methanol, potassium hydroxide, Varespladib Biological Activity propidium iodide (PI), RPMI 1640 medium, squalene, and terbinafine hydrochloride had been acquired from Sigma-Aldrich (Steinheim, Arimoclomol Metabolic Enzyme/Protease Germany). Phosphate buffered saline (PBS) was bought from Gibco (Gibco, HK, China) and (Ca2+ )-free PBS from Biomed (Lublin, Poland). Pancoll Human (1.077 g/mL) was bought from GmbHPANBiotech (Aidenbach, Germany). Penicillin and streptomycin had been acquired from Biowest (Nauill France). Lipopolysaccharide (LPS) from Escherichia coli 0111:B4 was bought from Merck (Kenilworth, NJ, USA). Human ELISA sets (IL-1, IL-8, TNF-) were purchased from BD Biosciences (Franklin Lake, NJ, USA). Sabouraud dextrose agar (SDA) and potato dextrose agar (PDA) had been from Biolab (Budapest, Hungary). 4.2. Plant Material, Extra.